Bundle-specific associations between white matter microstructure and Aβ and tau pathology in preclinical Alzheimer's disease
- McGill University, Canada
- Université de Sherbrooke, Canada
- Montreal Neurological Institute and Hospital, Canada
- Ludwig-Maximilians-Universität München, Germany
- Osaka City University Medical School, Japan
- University of Ulsan College of Medicine, Asan Medical Center, Republic of Korea
- Indiana University, United States
- Neuroscience Research Australia, Australia
- Harvard Medical School, Massachusetts General Hospital, United States
- University of Melbourne, Australia
- Washington University School of Medicine, United States
Abstract
Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer's disease (AD), are believed to spread through connected regions of the brain. Combining diffusion imaging and positron emission tomography, we investigated associations between white matter microstructure specifically in bundles connecting regions where Aβ or tau accumulates and pathology. We focussed on free-water corrected diffusion measures in the anterior cingulum, posterior cingulum, and uncinate fasciculus in cognitively normal older adults at risk of sporadic AD and presymptomatic mutation carriers of autosomal dominant AD. In Aβ-positive or tau-positive groups, lower tissue fractional anisotropy and higher mean diffusivity related to greater Aβ and tau burden in both cohorts. Associations were found in the posterior cingulum and uncinate fasciculus in preclinical sporadic AD, and in the anterior and posterior cingulum in presymptomatic mutation carriers. These results suggest that microstructural alterations accompany pathological accumulation as early as the preclinical stage of both sporadic and autosomal dominant AD.
Data availability
All raw imaging data from PREVENT-AD is openly available to researchers on the data repository https://registeredpreventad.loris.ca/
Article and author information
Author details
Alexa Pichet Binette
Funding
Canadian Institutes of Health Research (PJT-162091)
- Sylvia Villeneuve
Canadian Institutes of Health Research (PJT- 148963)
- Sylvia Villeneuve
Levesque Foundation
- Judes Poirier
Douglas Hospital Research Centre and Foundation
- John CS Breitner
Canada Foundation for Innovation
- Sylvia Villeneuve
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Morgan Barense, University of Toronto, Canada
Ethics
Human subjects: The study was approved by the ethics committee of the Faculty of Medicine of McGill University and of the Douglas Mental Health University Institute. Informed consent was obtained from all PREVENT-AD and DIAN participants prior to enrolling in the respective studies.We had access to the DIAN data with approval from DIAN leaders (data request DIAN-D1624).
Version history
- Received: September 9, 2020
- Accepted: May 12, 2021
- Accepted Manuscript published: May 13, 2021 (version 1)
- Version of Record published: June 1, 2021 (version 2)
Copyright
© 2021, Pichet Binette et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Bundle-specific associations between white matter microstructure and Aβ and tau pathology in preclinical Alzheimer's disease
eLife 10:e62929.
https://doi.org/10.7554/eLife.62929
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